Status asthmaticus (SA) is a sudden respiratory failure characterized by an acute bronchospasm with a severe inflammation, requiring in some cases mechanical ventilation (MV). Initial postmortem studies emphasized the presence of eosinophils in the bronchial wall and of mucus plugs filling the bronchi. More recently a prominent neutrophil influx was observed in patients with fatal or near fatal asthma. The aim of our study was to evaluate characteristics of bronchial inflammation in terms of cellular influx, mediators, cytokines and chemokines. Ten patients with SA were compared with 11 patients with chronic asthma, 4 without preexisting pulmonary disease requiring MV and 8 healthy subjects. Bronchial lavages in SA were indicated to remove bronchial plugs in case of atelectasia and/or refractory SA. The main findings in patients with SA were a massive influx of neutrophils (81.5 ± 4.5%) with a dramatic increase of neutrophil elastase. Although more limited than the neutrophil influx, eosinophils were present and associated with high levels of eosinophil cationic protein (ECP), which suggested that a part of the eosinophils were activated and degranulated. In parallel to the neutrophil and eosinophil influx, we observed elevated amounts of proinflammatory (IL-1β, IL-5, IL-6, TNFα) and anti-inflammatory (IL-10, IL-1 receptor antagonist, soluble TNF receptors) cytokines with a balance in favor of a net proinflammatory activity. Chemokines were also present in large quantities with a predominance of MCP-1, MIP-α and RANTES with a significant correlation between MCP-1, RANTES, IL-5 and both eosinophil and ECP values. In addition an acute 10- to 160-fold increase of 92-kD gelatinase (MMP9) was detected in bronchial lavage fluid from patients with SA associated with a free metallogelatinolytic activity, suggesting an imbalance in the local production of proteases and antiproteases. Therefore, our results indicate that the bronchi in SA are the site of an intense production of pro- and anti-inflammatory cytokines and chemokines that are implicated in the influx of eosinophils and neutrophils. The inflammatory pattern in SA clearly differs from the usual profile observed in chronic asthma.

Corbridge TC, Hall JB: The assessment and management of adults with status asthmaticus. Am J Respir Crit Care Med 1995;151:1296–1316.
Carroll N, Elliot J, Morton A, James A: The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993;147:405–410.
Sur S, Crotty TB, Kephart GM, Hyma BA, Colby TV, Reed CE, Hunt LW, Gleich GJ: Sudden onset fatal asthma: Distinct entity with few eosinophils and relatively more neutrophils in the airway mucosa. Am Rev Respir Dis 1993;148:713–719.
Lamblin C, Gosset P, Tillie-Leblond I, Saulnier F, Marquette CH, Wallaert B, Tonnel AB: Bronchial neutrophilia in patients with noninfectious status asthmaticus. Am J Respir Crit Care Med 1998;157:359–402.
Tillie-Leblond I, Hammad H, Desurmont S, Pugin J, Walllaert B, Tonnel AB, Gosset P: CC chemokines and IL-5 in bronchial lavages from status asthmaticus patients: Potential implication in eosinophil recruitment. Am J Respir Crit Care Med 2000;162:582–592.
Gonzalo JA, Lloyd CM, Wen D, Albar JP, Wells TN, Proudfoot A, Martinez AC, Dorf M, Bjerke T, Coyle AJ, Gutierrez-Ramos JC: The coordinated action of C-C chemokines in the lung orchestrates allergic inflammation. J Exp Med 1998;188:157–167.
Tillie-Leblond I, Pugin J, Marquette CH, Lamblin C, Saulnier F, Brichet A, Wallaert B, Tonnel AB, Gosset P: Balance between proinflammatory cytokines and their inhibitors in bronchial lavages from patients with status asthmaticus. Am J Respir Crit Care Med 1999;159:487–494.
Pugin J, Ricou B, Steinberg KP, Suter PM, Martin TR: Proinflammatory activity of bronchoalveolar lavage fluids from patients with ARDS, a prominent role for IL-1. Am J Respir Crit Care Med 1996;153:1850–1856.
Gosset P, Tsicopoulos A, Wallaert B, Vannimenus C, Joseph M, Tonnel AB, Capron A: Increased secretion of TNF alpha and IL-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol 1991;88:561–572.
Lemjabbar H, Gosset P, Lamblin C, Tillie I, Hartmann D, Wallaert B, Tonnel AB, Lafuma C: Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation during status asthmaticus. Am J Respir Crit Care Med 1999;159:1298–1307.
Yao PM, Buhler JM, D’Ortho MP, Lebargy F, Delclaux C, Harf A, Lafuma C: Expression of matrix metalloproteinase gelatinase A and B by cultured epithelial cells from human bronchial explants. J Biol Chem 1996;271:15580–15589.
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